Age-related Infectious Diseases

Aging is associated with both a decline in the function of an organism and a greater risk for contracting infectious diseases. Many countries are now facing increased elderly populations and high prevalences of fatal age-related infectious pulmonary diseases, such as COPD and bacterial and fungal pneumonia, and non-respiratory infections such as periodontitis.

There are three main reasons why existing antibiotics are ineffective in treating age-related infections:

Age-related immunosuppression

Development of drug resistance

The formation of bacterial biofilms, which are only affected by concentrations of antibiotics that can not be reached at the site of infection

Mixed infections

IHM specialists are focused on isolating and studying previously unknown causative agents of age-related infectious diseases and developing novel ways to control these organisms.

PRIMARY DIRECTIONS OF THE RESEARCH

Novel Pathogens Search

The IHM applies innovative approaches at the forefront of technology to identify and isolate novel causative agents of age-related infectious diseases, as each newly identified pathogen comprises a significant step towards being able to prevent and/or enhance the efficacy of treatments for age-related infectious pathologies.

Novel Therapeutic Directions

Through our interdisciplinary studies, we anticipate being able to translate our research findings into potential therapeutic drugs for age-related respiratory tract infections, such as COPD and fungal pneumonia, and other non-respiratory pathologies, including periodontitis. Our ultimate goal is to make these therapies available to the entire human community and thereby effectively increase the human lifespan.

READ MORE

We try to make our data available to the whole scientific community. The HMI welcomes collaborative studies to unravel the pathogenesis of human diseases associated with the microbiota. However, we ask that you respect the rights of first publication and cite our work as follows:

In vitro antimicrobial activity of a novel compound, Mul-1867, against clinically important bacteria.

Antimicrobial resistance and infection control (2015)

In vitro antimicrobial activity of a novel compound, Mul-1867, against clinically important bacteria.

Publication Type

Journal Article

Authors

George Tetz

Victor Tetz

Abstract

Background

The antimicrobial activity of Mul-1867, a novel synthetic compound, was tested against 18 bacterial strains, including clinical isolates and reference strains from culture collections.

Methods

The minimal inhibitory concentration (MICs) and minimal bactericidal concentration (MBCs) were determined by using the broth macrodilution method. The kinetics of the inhibitory effects of Mul-1867 against biofilm-growing microorganisms was assessed at time-kill test in vitro against 48-h-old biofilms of Staphylococcus aureus and Escherichia coli. Transmission electron microscopy analyses was conducted to examine cell disruption.

Results

A comparative assessment of the antimicrobial activities of Mul-1867 and chlorhexidine digluconate (CHG), used as a control antimicrobial, indicated that Mul-1867 was significantly more effective as a disinfectant than CHG. Mul-1867 showed potent antimicrobial activities against all the tested bacteria (MIC: 0.03–0.5 μg/mL). Furthermore, MBC/MIC ratio of Mul-1867 for all tested strains was less than or equal to 4. Time-kill studies showed that treatment with Mul-1867 (0.05–2 %) reduced bacterial numbers by 2.8–4.8 log10 colony forming units (CFU)/mL within 15–60 s. Bactericidal activity of Mul-1867 was confirmed by morphological changes revealed by TEM suggested that the killing of bacteria was the result of membrane disruption.

Conclusion

Overall, these data indicated that Mul-1867 may be a promising antimicrobial for the treatment and prevention of human infections.

There is an urgent need for new antimicrobial compounds to treat various lung infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-PA).

Methods

We studied the potency of Mul-1867 against MDR-PA isolates from patients with cystic fibrosis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia. The minimal inhibitory concentrations (MICs) and minimum biofilm eliminating concentrations (MBECs), defined as the concentrations of drug that kill 50 % (MBEC50), 90 % (MBEC90), and 100 % (MBEC100) of the bacteria in preformed biofilms, were determined by using the broth macrodilution method.

Results

Mul-1867 exhibited significant activity against MDR-PA and susceptible control strains, with MICs ranging from 1.0 to 8.0 µg/mL. Mul-1867 also possesses anti-biofilm activity against mucoid and non-mucoid 24-h-old MDR-PA biofilms. The MBEC50 value was equal to onefold the MIC. The MBEC90 value ranged from two to fourfold the MIC. Moreover, Mul-1867 completely eradicated mature biofilms at the concentrations tested, with MBEC100 values ranging between 16- and 32-fold the MIC. Mul-1867 was non-toxic to Madin-Darby canine kidney (MDCK) cells at concentrations up to 256 µg/mL.

Conclusion

Overall, these data indicate that Mul-1867 is a promising locally acting antimicrobial for the treatment and prevention of P. aeruginosa infections.

The polymicrobial nature in pulmonary infections in patients with CF is one the causes of the lack of efficacy of existing antibiotic treatment. The aim of the present study was to evaluate clinical efficacy of nebulized solution of novel antimicrobial drug candidate Mul-1867 (Poly-N,N-hexamethyleneguanidine, modified by hydrazine) in murine pneumonia model caused by mixed infection.

Methods

8-weeks old C57BL/6 mice were intranasally infected with P. aeruginosa + S. aureus (each 1×105 cfu/mouse) or P. aeruginosa +C. albicans (each 1×105 cfu/mouse) mix. Treatment was started 12 h after infection with Mul-1867 or Amikacin (taken as representative of aminoglycosides that are used for the treatment of lung infections in CF patients), both administered by intranasal inhalation at 32×MIC.

Results

Mul-1867 exhibited a high level of antimicrobial activity with the MIC 0.25 mg/L against S.aureus; 0.5 mg/L against C. albicans and
4.0 mg/L against P. aeruginosa. Amikacin was less active; the MICs 128 mg/L for both S.aureus and P. aeruginosa and was not active
against C. albicans. Induced pneumonia displayed a total death of control animals without of treatment within 72 h post-infection in both groups with mixed infections. For the group P. aeruginosa + S. aureus treated with Mul-1867 to the end of observation period (72 h) 20% of mice died. Only 10% animals died in P.aeruginosa + C. albicans group treated
with Mul-1867. Animals treated with Amikacin displayed 50% mortality in P. aeruginosa + S.aureus group and 70% mortality in P.aeruginosa + C. albicans.